Migraine is a condition that affects approximately 28 million people in the United States, with females more frequently affected than males (Silberstein, Neurology, 2000 55:754-63). Migraine headache is associated with a painful vasodilation of cranial vessels that typically manifests in unilateral, pulsating pain of moderate or severe intensity that worsens with physical activity and typically lasts from 4 to 72 hours. In addition to headache pain, migraine can be associated with a variety of other symptoms including nausea, vomiting, phonophobia and photophobia (Lawrence, Southern Medical Journal, 2004, 97(11):1069-77). Approximately 20% of migraineurs experience an aura, which typically includes visual symptoms, such as spots of light, zigzag lines or a graying out of vision. Migraines may be triggered by a variety of factors, including stress, diet/foods, shifts in time schedules, body rhythms, sleep patterns, changes in weather/barometric pressure, changes in altitude and hormonal changes.
Mild migraine can sometimes be treated with over-the-counter medications such as aspirin, acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs) and combination products that include caffeine. Triptans may relieve up to 80% of migraines within two hours (Scholpp et al, Cephalalgia, 2004, 24:925-33). Seven different triptans have been approved and are currently marketed and are available in the United States in a variety of formulations, such as oral, dissolvable, nasal spray and injectable.
Sumatriptan is indicated for the acute treatment of migraine attacks, with our without aura, in adults. Sumatriptan is a serotonin agonist for a vascular 5-hydroxytriptamine1D (5-HT1D) receptor subtype (a member of the 5-HT1 family) and its therapeutic activity in migraine is generally attributed this agonist activity. Currently, it is available in three formulations: oral, injectable and nasal. While oral administration of sumatriptan tablets is typically well tolerated, oral administration suffers from inconsistent bioavailability and efficacy, partly due to variable presystemic hepatic metabolism. Injectable sumatriptan may be fast acting, but it is also short-lived. Sumatriptan nasal spray is more variable than the injectable form and is associated with side effects, e.g. bitter taste, which some patients find intolerable.